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Influenza polymerase

Ki Hyun Seo, Da Jeong Bae, Ji Na Kim, Ho Sung Lee, Yong Hoon Kim, Jong Sook Park, Myung Shin Kim, Hun Soo Chang, Ji Hye Son, Dong Gyu Baek, Jun Suk Lee, Choon Sik Park
PURPOSE: Viral infections are involved in ~50% of exacerbations among Caucasian adult asthmatics. However, there have been few reports on the causative virus of exacerbations in Korean adult asthmatics. Thus, we compared frequencies and types of viruses between lower respiratory tract illnesses (LRTIs) with exacerbations (exacerbated LRTIs) and those without exacerbations (stable LRTIs) to evaluate contribution of respiratory viruses to exacerbations. METHODS: Viral RNA was extracted from sputum using the Viral Gene-spin™ Kit...
November 2017: Allergy, Asthma & Immunology Research
Seongjun Chu, Sang Joon Park, So My Koo, Yang Ki Kim, Ki Up Kim, Soo Taek Uh, Tae Hyung Kim, Suyeon Park
BACKGROUND: Most patients with influenza recover spontaneously or following treatment with an anti-viral agent, but some patients experience pneumonia requiring hospitalization. We conducted a retrospective review to determine the incidence and risk factors of pneumonia in hospitalized patients with influenza A or B. METHODS: A total of 213 patients aged 18 years or older and hospitalized with influenza between January 2012 and January 2015 were included in this study...
September 1, 2017: Tuberculosis and Respiratory Diseases
Hwa Sik Jung, Byung Ju Kang, Seung Won Ra, Kwang Won Seo, Yangjin Jegal, Jae Bum Jun, Jiwon Jung, Joseph Jeong, Hee Jeong Jeon, Jae Sung Ahn, Taehoon Lee, Jong Joon Ahn
BACKGROUND: Bacterial pneumonia occurring after respiratory viral infection is common. However, the predominant bacterial species causing pneumonia secondary to respiratory viral infections other than influenza remain unknown. The purpose of this study was to know whether the pathogens causing post-viral bacterial pneumonia vary according to the type of respiratory virus. METHODS: Study subjects were 5,298 patients, who underwent multiplex real-time polymerase chain reaction for simultaneous detection of respiratory viruses, among who visited the emergency department or outpatient clinic with respiratory symptoms at Ulsan University Hospital between April 2013 and March 2016...
September 1, 2017: Tuberculosis and Respiratory Diseases
Patricia Domingues, Benjamin G Hale
Host restriction of influenza A virus limits pandemic emergence. The viral RNA polymerase (vPol) is an essential enzyme that must adapt for avian viruses to replicate in humans. Species differences in host ANP32A dictate adaptation: human ANP32A lacks an uncharacterized 33 amino-acid insertion that is present in avian ANP32A. Here, we uncover important contributions of host SUMOylation to vPol activity, including avANP32A function. We also identify a hydrophobic SUMO interaction motif (SIM)-like sequence unique to avANP32A that critically supports avian-signature vPol...
September 12, 2017: Cell Reports
Serena Massari, Jenny Desantis, Giulio Nannetti, Stefano Sabatini, Sara Tortorella, Laura Goracci, Violetta Cecchetti, Arianna Loregian, Oriana Tabarrini
Two facile and efficient one-step procedures for the regioselective synthesis of 7-aryl-5-methyl- and 5-aryl-7-methyl-2-amino-[1,2,4]triazolo[1,5-a]pyrimidines have been developed, via reactions of 3,5-diamino-1,2,4-triazole with variously substituted 1-aryl-1,3-butanediones and 1-aryl-2-buten-1-ones, respectively. The excellent yield and/or regioselectivity shown by the reactions decreased when ethyl 5-amino-1,2,4-triazole-3-carboxylate was used. [1,2,4]Triazolo[1,5-a]pyrimidine being a privileged scaffold, the procedures herein reported may be useful for the preparation of biologically active compounds...
September 13, 2017: Organic & Biomolecular Chemistry
Alex W H Chin, Nathaniel K C Leong, John M Nicholls, Leo L M Poon
The 701 and 702 positions of influenza PB2 polymerase subunit are previously shown to have roles on host range. Limited polymorphisms at these two residues are identified in natural isolates, thereby limiting the study of their role in the polymerase. In this study, we generated 31 viable viruses by random mutagenesis at this region, indicating that these positions can tolerate a wide range of amino acids. These mutants demonstrated varying polymerase activities and viral replication rates in mammalian and avian cells...
September 12, 2017: Scientific Reports
Megan L Shaw
Options for influenza therapy are currently limited to one class of drug, the neuraminidase inhibitors. Amidst concerns about drug resistance, much effort has been placed on the discovery of new drugs with distinct targets and mechanisms of action, with great success. There are now several candidates in late stage development which include small molecules targeting the three subunits of the viral polymerase complex and monoclonal antibodies targeting the hemagglutinin, as well as host-directed therapies. The availability of drugs with diverse mechanisms now opens the door to exploring combination therapies for influenza, and the range of administration routes presents more opportunities for treating hospitalized patients...
September 11, 2017: ACS Infectious Diseases
Pavel Goriacko, Lisa Saiman, Philip Zachariah
BACKGROUND: Multiplex polymerase chain reaction (mPCR) based methods are increasingly used to detect respiratory pathogens in children. While rapid identification of viruses has been shown to reduce antibiotic use, the impact of detecting specific viruses on antibiotic utilization has not been ascertained. This study compared antibiotic utilization among hospitalized children who tested positive for different respiratory viruses at admission. METHODS: A single-center study of hospitalized children under 21 years of age who tested positive at admission for at least one respiratory virus by mPCR from October 1 2012 to October 1 2015 was performed...
September 5, 2017: Pediatric Infectious Disease Journal
Mark Zanin, Sook-San Wong, Subrata Barman, Challika Kaewborisuth, Peter Vogel, Adam Rubrum, Daniel Darnell, Atanaska Marinova-Petkova, Scott Krauss, Richard J Webby, Robert G Webster
North American wild birds are an important reservoir of influenza A viruses, yet the potential of viruses in this reservoir to transmit and cause disease in mammals is not well understood. Our surveillance of avian influenza viruses (AIVs) at Delaware Bay, USA, revealed a group of similar H1N1 AIVs isolated in 2009, some of which were airborne-transmissible in the ferret model without prior adaptation. Comparison of the genomes of these viruses revealed genetic markers of airborne transmissibility in the Polymerase Basic 2 (PB2), PB1, PB1-F2, Polymerase Acidic-X (PA-X), Nonstructural Protein 1 (NS1), and Nuclear Export Protein (NEP) genes...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
Su-Jin Park, Eun-Ha Kim, Hyeok-Il Kwon, Min-Suk Song, Se Mi Kim, Young-Il Kim, Young-Jae Si, In-Won Lee, Hiep Dinh Nguyen, Ok Sarah Shin, Chul-Joong Kim, Young Ki Choi
Recently identified highly pathogenic avian influenza (HPAI) H5N8 viruses (clade are relatively low to moderately pathogenic in mammalian hosts compared to HPAI H5N1 viruses. In this study, we generated reassortant viruses comprised of A/MD/Korea/W452/2014(H5N8) with substitution of individual genes from A/EM/Korea/W149/2006(H5N1) to understand the contribution of each viral gene to virulence in mammals. Substituting the PB2 gene segment or the NA gene segment of the H5N8 virus by that from the H5N1 virus resulted in significantly enhanced pathogenicity compared with the parental H5N8 virus in mice...
September 5, 2017: Virulence
Joanna Merckx, Rehab Wali, Ian Schiller, Chelsea Caya, Genevieve C Gore, Caroline Chartrand, Nandini Dendukuri, Jesse Papenburg
Background: Rapid and accurate influenza diagnostics can improve patient care. Purpose: To summarize and compare accuracy of traditional rapid influenza diagnostic tests (RIDTs), digital immunoassays (DIAs), and rapid nucleic acid amplification tests (NAATs) in children and adults with suspected influenza. Data Sources: 6 databases from their inception through May 2017. Study Selection: Studies in English, French, or Spanish comparing commercialized rapid tests (that is, providing results in <30 minutes) with reverse transcriptase polymerase chain reaction reference standard for influenza diagnosis...
September 19, 2017: Annals of Internal Medicine
Wentian Chen, Qi Xu, Yaogang Zhong, Hanjie Yu, Jian Shu, Tianran Ma, Zheng Li
The RNA polymerase complex (RNApc) in influenza A viruses (IVs) is composed of the PB2, PB1 and PA subunits, which are encoded by the three longest genome segments (Seg1-3) and are responsible for the replication of vRNAs and transcription of viral mRNAs. However, the co-evolutionary relationships of the three segments from the known 126 subtypes IVs are unclear. In this study, we performed a detailed analysis based on a total number of 121,191 nucleotide sequences. Three segment sequences were aligned before the repeated, incomplete and mixed sequences were removed for homologous and phylogenetic analyses...
August 31, 2017: Virology
Siddhant Datta, Edward E Walsh, Derick R Peterson, Ann R Falsey
Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of adult respiratory illness. We evaluated routine viral testing and discharge diagnoses for identifying RSV and influenza burden. Polymerase chain reaction results performed in adults during emergency room visits or hospitalizations were reviewed. Peak RSV activity preceded influenza activity by 8 weeks. The ratio of total number of viral tests performed divided by total number of respiratory visits was higher during influenza than RSV peaks (1...
June 1, 2017: Journal of Infectious Diseases
Chung-Young Lee, Se-Hee An, Ilhwan Kim, Du-Min Go, Dae-Yong Kim, Jun-Gu Choi, Youn-Jeong Lee, Jae-Hong Kim, Hyuk-Joon Kwon
The polymerase of avian influenza A virus (AIV) is a heterotrimer composed of PB2, PB1, and PA. PB2 plays a role in overcoming the host barrier; however, the genetic prerequisites for avian PB2 to acquire mammalian pathogenic mutations have not been well elucidated. Previously, we identified a prototypic avian PB2 that conferred non-replicative and non-pathogenic traits to a PR8-derived recombinant virus when it was used to infect mice. Here, we demonstrated that key amino acid mutations (I66M, I109V, and I133V, collectively referred to as MVV) of this prototypic avian PB2 increase the replication efficiency of recombinant PR8 virus carrying the mutated PB2 in both avian and mammalian hosts...
August 31, 2017: Scientific Reports
Liji Xie, Zhixun Xie, Li Huang, Sheng Wang, Jiaoling Huang, Yanfang Zhang, Tingting Zeng, Sisi Luo
Sequence analysis of duck plague virus (DPV) revealed that there was a 528bp (B fragment) deletion within the UL2 gene of DPV attenuated vaccine strain in comparison with field virulent strains. The finding of gene deletion provides a potential differentiation test between DPV virulent strain and attenuated strain based on their UL2 gene sizes. Thus we developed a polymerase chain reaction (PCR) assay targeting to the DPV UL2 gene for simultaneous detection of DPV virulent strain and attenuated strain, 827bp for virulent strain and 299bp for attenuated strain...
August 30, 2017: Journal of Virological Methods
Chung-Young Lee, Hyuk-Joon Kwon, Thanh Trung Nguyen, Ilhwan Kim, Hyung-Kwan Jang, Jae-Hong Kim
Twelve nucleotides located at the 3' end of viral genomic RNA (vRNA) are conserved among influenza A viruses (IAV) and have a promoter function. Hoffmann's 8-plasmid reverse genetics vector system introduced mutations at position 4, C nucleotide (C4) to U nucleotide (U4), of the 3' ends of neuraminidase (NA) and matrix (M) vRNAs of wild-type A/PR/8/34 (PR8). This resulted in a constellation of C4 and U4 vRNAs coding for low (polymerases) and relatively high (all others) copy number proteins, respectively. U4 has been reported to increase promoter activity in comparison to C4, but the constellation effect on the replication efficiency and pathogenicity of reverse genetics PR8 (rgPR8) has not been fully elucidated...
August 31, 2017: Journal of Veterinary Science
Jin-Wook Jang, Chung-Young Lee, Il-Hwan Kim, Jun-Gu Choi, Youn-Jeong Lee, Seong-Su Yuk, Ji-Ho Lee, Chang-Seon Song, Jae-Hong Kim, Hyuk-Joon Kwon
A/Puerto Rico/8/34 (PR8)-derived recombinant viruses have been used for seasonal flu vaccines; however, they are insufficient for vaccines against some human-fatal H5N1 highly pathogenic avian influenza (HPAI) viruses (HPAIV) due to low productivity. Additionally, the polymerase basic 2 (PB2) protein, an important mammalian-pathogenicity determinant, of PR8 possesses several mammalian-pathogenic mutations. We previously reported two avian PB2 genes (01310 and 0028) related to efficient replication in embryonated chicken eggs (ECEs) and nonpathogenicity in BALB/c mice...
August 31, 2017: Journal of Veterinary Science
Herve Caspard, Raburn M Mallory, Jing Yu, Christopher S Ambrose
BACKGROUND: This systematic review and meta-analysis describes and consolidates findings from all studies that assessed the effectiveness of live-attenuated influenza vaccine (LAIV) against laboratory-confirmed influenza since the 2009 pandemic in children and young adults. METHODS: A MEDLINE search was conducted for articles published from January 1, 2010 to November 30, 2016. All original publications reporting an effectiveness estimate of LAIV against cases of influenza confirmed by reverse-transcription polymerase chain reaction or culture were retained for analysis...
2017: Open Forum Infectious Diseases
Minna Haimi-Hakala, Outi Hälli, Tapio Laurila, Mirja Raunio-Saarnisto, Tiina Nokireki, Taina Laine, Suvi Nykäsenoja, Kirsti Pelkola, Joaquim Segales, Marina Sibila, Claudio Oliviero, Olli Peltoniemi, Sinikka Pelkonen, Mari Heinonen
BACKGROUND: The objective of our study was to clinically and etiologically investigate acute outbreaks of respiratory disease in Finland. Our study also aimed to evaluate the clinical use of various methods in diagnosing respiratory infections under field conditions and to describe the antimicrobial resistance profile of the main bacterial pathogen(s) found during the study. METHODS: A total of 20 case herds having finishing pigs showing acute respiratory symptoms and eight control herds showing no clinical signs suggesting of respiratory problems were enrolled in the study...
2017: Porcine Health Management
Xiaolei Ma, Lili Xie, Charles Wartchow, Robert Warne, Yongjin Xu, Alexey Rivkin, David Tully, Steven Shia, Kyoko Uehara, Dianna M Baldwin, Gladys Muiru, Weidong Zhong, Isabel Zaror, Dirksen E Bussiere, Vincent H J Leonard
Influenza virus uses a unique mechanism to initiate viral transcription named cap-snatching. The PB2 subunit of the viral heterotrimeric RNA polymerase binds the cap structure of cellular pre-mRNA to promote its cleavage by the PA subunit. The resulting 11-13 capped oligomer is used by the PB1 polymerase subunit to initiate transcription of viral proteins. VX-787 is an inhibitor of the influenza A virus pre-mRNA cap-binding protein PB2. This clinical stage compound was shown to bind the minimal cap-binding domain of PB2 to inhibit the cap-snatching machinery...
August 24, 2017: Scientific Reports
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